Antibody variants formed during cell culture fermentation have been known to impact the downstream conjugation process of antibody-drug conjugates (ADCs), affecting ADC product quality. Trisulfides, a posttranslational modification commonly found in immunoglobulin G (IgG) antibodies, not only directly influence the antibody reduction step, but were also found to be indirectly responsible for the formation of a new free drug impurity during conjugation. Novel processing methods were evaluated to prevent formation of the new impurity, or to remove it in the downstream steps. This presentation will: -Describe the relationship between trisulfides and the appearance of an unexpected free drug impurity, -Review mitigation methods evaluated to address the new conjugation process impurity, and -Increase awareness regarding the potential for antibody variants to play an unanticipated role in multiple conjugation process steps. Through the analysis of the reported mitigation efforts, conjugation process development groups can become informed of unique impurity removal approaches as additional tools to meet novel impurity challenges, while continuing to consider the at times unpredictable role antibody variants can play in ADC conjugation.

Mitigating novel ADC impurity challenges through creative approaches: Check the antibody variants

251st National Meeting (2016)

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